There are three primary structures within the human eye that are essential to vision and subject to age-related damage: the cornea, lens and retina. The retina is a multi-layered sensory tissue that lines the back of the eye. It contains millions of photoreceptors that capture light rays and convert them into electrical impulses. These impulses travel along the optic nerve to the brain where they are turned into images. There are two types of photoreceptors in the retina: rods and cones. The retina contains approximately 6 million cones. The cones are contained in the macula, the portion of the retina responsible for central vision. They are most densely packed within the fovea, the very center portion of the macula. Cones function best in bright light and allow us to appreciate color. There are approximately 125 million rods. They are spread throughout the peripheral retina and function best in dim lighting. The rods are responsible for peripheral and night vision. The retina is essential for vision and is easily damaged by prolonged unprotected exposure to visible and near visible light. Light-induced retinal pathologies include cystoid macular oedema, solar retinopathy, ocular melanomas and age-related macular degeneration (ARMD). Light-induced retinal damage is classified as structural, thermal or photochemical and is largely determined by the exposure time, power level and wavelength of light.
In healthy adults the retina is generally protected from the most severe forms of light-induced damage by the outer eye structures, including the cornea and crystalline lens. The cornea is a transparent proteinaceous ocular tissue located in front of the iris and is the only transparent eye structure exposed directly to the external environment. The cornea is essential for protecting the delicate internal structures from damage and facilitates the transmission of light through the aqueous humor to the crystalline lens.
The crystalline lens is an accommodating biological lens lying in back of the cornea, anterior chamber filled with aqueous humor, and the iris. Between the lens and the retina is the vitreous chamber filled with vitreous humor. The optical pathway through the eye acts to refract the light entering the eye, with the cornea providing most of the optical power, and the accommodating lens facilitating the convergence of both far and near images onto the retina. Ocular elements in the optical pathway absorb various wavelengths of light, while permitting others to pass through. In the normal human eye, only wavelengths of light between about 400 nm and 1,400 nm can pass through the refracting elements of the eye to the retina. However, high transmittance levels of blue and violet light (wavelengths from about 390 nm to about 500 nm) has been linked to conditions such as retinal damage, macular degeneration, retinitis pigmentosa, and night blindness.
Intraocular pressure (IOP) in the eye can significantly affect the elements of the ocular pathway, and is maintained by the formation and drainage of aqueous humor, a clear, colorless fluid that fills the anterior and posterior chambers of the eye. Aqueous humor normally flows from the anterior chamber of the eye out through an aqueous outflow channel at a rate of 2 to 3 microliters per minute.
Glaucoma, for example, is a progressive disease of the eye characterized by a gradual loss of nerve axons at the optic nerve head. In many cases, the damage to the optic nerve head is due to increased intraocular pressure. This increase in pressure is most commonly caused by stenosis or blockage of the aqueous outflow channel, resulting in excessive buildup of aqueous fluid within the eye. Other causes include increase in venous pressure outside the eye which is reflected back through the aqueous drainage channels and increased production of aqueous humor. In a “normal” eye, IOP ranges from 8 to 21 mm mercury. In an eye with glaucoma, IOP can range between normal pressures up to as much as 50 mm mercury. This increase in IOP produces gradual and permanent loss of vision in the afflicted eye.
Existing corrective methods for the treatment of glaucoma include drugs, surgery, and implants. In many cases therapy can require delivery of various therapeutic agents to various portions of the eye over a lengthy period of time, typically by injection of the agent directly into the eye.
There are numerous examples of surgical procedures that have been developed in an effort to treat victims of glaucoma. An iridectomy, removal of a portion of the iris, is often used in angle-closure glaucoma wherein there is an occlusion of the trabecular meshwork by iris contact. Removal of a piece of the iris then gives the aqueous humor free passage from the posterior to the anterior chambers in the eye. A trabeculotomy, opening the inner wall of Schlemm's canal, is often performed in cases of developmental or juvenile glaucoma so as to increase the outflow of the aqueous humor, thereby decreasing IOP. In adults, a trabeculectomy shunts fluid through a trapdoor flap in the eye that performs a valve-like function for the first few weeks after surgery.
While often successful, these surgical techniques possess inherent risks associated with invasive surgery on an already afflicted or compromised eye. Furthermore, the tissue of the eye can scar over this small area and the eye reverts to the pre-operative condition, thereby necessitating the need for further treatment.
Ocular implants are sometimes used in long-term glaucoma treatment. One early implant is called the Molteno Implant, after A. C. B. Molteno. The implant is a small circular plate with a rigid translimbal drainage tube attached. The plate was 8.5 mm in diameter and formed a surface area of about 100 mm2. This implant is sutured to the sclera in the anterior segment of the eye near the limbus and the drainage tube is inserted into the anterior chamber of the eye. Once implanted, the body forms scar tissue around the plate. Fluid causes the tissue above the plate to lift and form a bleb into which aqueous humor flows from the anterior chamber via the drainage tube. A bleb is a fluid filled space surrounded by scar tissue, somewhat akin to a blister. The fluid within the bleb then flows through the scar tissue, at a rate which can regulate IOP.
A newer implant has been redesigned for insertion into the posterior segment of the eye to avoid problems with early designs. This implant is referred to as a long tube Molteno implant. The implant comprises a flexible drainage tube connected to one or more rigid plate reservoirs. The plates are shaped to conform to the curvature of the eye. The reservoir plate is placed under Tenon's capsule in the posterior segment of the eye and sutured to the sclera. The drainage tube is implanted into the anterior chamber through a scleral incision. However, the long tube Molteno implant is still disadvantageous, as the plates are formed of a rigid plastic which makes insertion beneath the eye tissue difficult and time-consuming.
After such an implant is attached, IOP tends to fall as aqueous fluid flows immediately through the drainage tube. However, an open drainage tube may release too much of the fluid too fast, which is detrimental to the eye. It is not until 2-6 weeks later that the bleb forms around the plate to sufficiently regulate the fluid flow. Some prior devices have therefore incorporated valves in the fluid drain path designed to function for a limited time until the bleb forms. However, such valved devices sometimes clog later, requiring another surgery.
More recently introduced implants feature a flexible plate that attaches to the sclera, and a drainage tube positioned for insertion into the anterior chamber of the eye. A bleb forms around the plate and fluid drains into and out of the bleb to regulate IOP. This type of shunt is called a Baerveldt shunt. One such device has an open tube with no flow restricting elements. Temporary sutures are used to restrict fluid flow for a predetermined period after which the bleb forms and fluid drainage is properly regulated. The temporary sutures are either biodegradable or removed in a separate procedure. This method works well, but the timing of suture dissolution is inexact and may operate improperly, and a second procedure undesirable.
Some shunts also include fenestrations through the plate to promote fibrous adhesion, which may reduce bleb height. Though a bleb is thought to have a beneficial function in regulating aqueous humor diffusion, too large of a bleb may cause the patient some pain or may be aesthetically unacceptable. Some doctors even prefer to use anti-proliferatives such as mitomycin C or 5-FU at the time of surgery to prevent formation of the fibrous bleb. Another potential complication is endophthalmitis, an inflammation of the internal tissue of the eye. This complication may occur in any intraocular surgery, with possible loss of vision and even of the eye itself. Infectious etiology is the most common cause, and various bacteria and fungi have been isolated as the cause of the endophthalmitis. The risk of infection is more pronounced early in a shunt implant procedure, when a passage to the interior of the eye is created and fluid flows therethrough. Later, the bleb acts as a filter to prevent microorganisms such as bacteria from entering the eye.
Some eye diseases can be treated with pharmaceuticals. However, where the diseases primarily affect the back of the eye, it can be difficult to administer and achieve effective levels of therapeutic agents in that portion of the eye. Such diseases are typically treated by direct injection of biologically active pharmaceutical agents, such as anti-inflammatory steroids and target-specific antibodies. Treatment may entail repeated injections that can put the patient at risk of complications involving conditions such as infection, endophthalmitis, high intraocular pressure (IOP), glaucoma, cataract, retinal detachment and bleeding, and lack of wound-healing. A new approach is needed that can deliver pharmaceuticals and the like to the back of the eye while mitigating the adverse effects that attend the prior art. However, any solutions requiring patient compliance or repeated injection run the risk of failure due to noncompliance of the patient.